76 articles - From Friday Jul 29 2022 to Friday Aug 05 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
| Lancet Haematol |
Suitability of haematopoietic cell donors: updated consensus recommendations from the WBMT standing committee on donor issues. Sections on communicable diseases, clonal haematopoiesis of indeterminate potential, paediatric aspects including psychological issues, and reporting on serious adverse events have been added. The intention of this Review is to support decision making, with the goal of minimising the medical risk to the donor and protecting the recipient from transmissible diseases. |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Blood |
Clonal germinal center B cells function as a niche for T-cell lymphoma. The genes expressed in aberrantly expanded GCB cells in murine tumors were also broadly expressed in the B-lineage cells of TET2-mutant human AITL. Therefore, ACH-derived GCB cells could undergo independent clonal evolution and support the tumorigenesis in AITL via the CD40-CD40LG axis. |
Cost Effectiveness of Second-Line Axicabtagene ciloleucel in Relapsed Refractory Diffuse Large B-cell Lymphoma. Routine usage of second-line CAR-T would add significantly to healthcare expenditures in the USA (>$1 billion each year), even when used in a high-risk subpopulation. Further reductions in the cost of CAR-T are needed to be affordable in many regions of the world. |
Dual-antigen targeted off-the-shelf NK cells show durable response and prevent antigen escape in lymphoma and leukemia. Furthermore, iDuo NK cells effectively eliminated both CD19+ and CD19- lymphoma cells and displayed a unique propensity for targeting malignant cells over healthy cells that expressed CD19, features not achievable with anti-CAR19 T cells. iDuo NK cells combined with therapeutic antibodies represents a promising approach to prevent relapse due to antigen loss and tumor heterogeneity in patients with B cell malignancies. |
Engineering Naturally Occurring CD7 Negative T Cells for the Immunotherapy of Hematological Malignancies. Additionally, samples from patients responsive to therapy had a higher proportion of CD7lo T cells than in non-responders. Thus, CARCD7- T cells have favorable biological characteristics and may present a promising T-cell subset for adoptive cell therapy of T-ALL and other hematological malignancies. |
Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas. Furthermore, other subgroups among aggressive peripheral T-cell lymphomas (PTCL) also expressed lower levels of CD48 than normal T-cells, suggesting that CD48 is a key molecule in malignant T-cell evasion of NK cell surveillance. Thus, this study demonstrates that CD48 expression is likely critical for malignant T-cell lymphoma cell regulation of NK cell mediated immunity and provides a rationale for future evaluation of CD48 as a molecular biomarker in NK cell-associated immunotherapies. |
Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism. These findings should be a call to action to increase awareness and provide evidence-based strategies for preventing and treating AUB in this setting. This was an academic study (NCT04748393 at no funding was received. |
MINIMAL RESIDUAL DISEASE-DRIVEN TREATMENT INTENSIFICATION WITH SEQUENTIAL ADDITION OF IBRUTINIB TO VENETOCLAX IN R/R CLL. This sequential MRD-guided approach led to uMRD4 in 33/38 patients (87%) with venetoclax monotherapy or combined with ibrutinib., delivering treatment combination only in a fraction, and ultimately identifying the few patients benefiting from continuous therapy. Clinical trial number: NCT04754035. |
Phase 3 Trial of Gilteritinib Plus Azacitidine Vs Azacitidine for Newly Diagnosed FLT3mut+ AML Ineligible for Intensive Chemotherapy. Results support the safety/tolerability and clinical activity of upfront therapy with GIL+AZA in older/unfit patients with FLT3mut+ AML. Clinical Trial # NCT02752035. |
| Blood Adv |
Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis. Using molecular, pharmacological and genetic approaches, we demonstrate that these RSPO3-induced hematopoietic phenotypes are Wnt and RSPO3 dependent and mediated through non-canonical Wnt signaling. Our study highlights a distinct role for a Wnt/RSPO3 signaling axis in the regulation of hematopoiesis, as well as possible challenges related to therapeutic usage of R-spondins for regenerative medicine. |
Enrichment of BTK Leu528Trp mutations in Patients with CLL on Zanubrutinib: Potential for Pirtobrutinib Cross Resistance. Both patients subsequently responded to venetoclax based treatment. In summary we have identified an enrichment of the BTK Leu528Trp mutation arising in patients treated with zanubrutinib which may impart cross-resistance to the non-covalent inhibitor pirtobrutinib and therefore implications for sequencing of these treatments in CLL. |
Second Malignancies among Older Patients with Classical Myeloproliferative Neoplasms Treated with Hydroxyurea. We did not identify significant differences in the incidence of solid or hematologic SM, including AML/MDS (HR=1.33, 95% CI: 0.77-2.29; p=0.30), between HU users and non-users. Our results suggest that the use of HU does not increase the risk of SM in older MPN patients. |
SUMOylation inhibition overcomes proteasome inhibitor resistance in multiple myeloma. Mechanistically, combination treatment with subasumstat and CFZ enhanced genotoxic and proteotoxic stress and induced apoptosis was associated with activity of the prolyl isomerase PIN1. In summary, our findings reveal activated SUMOylation as a therapeutic target in MM and point to combined SUMO/proteasome inhibition as a novel and potent strategy for the treatment of proteasome inhibitor-resistant MM. |
The interplay between GPIb/IX-antibodies, platelet hepatic sequestration, and TPO levels in patients with chronic ITP. In addition, platelet hepatic sequestration and TPO levels were positively associated. This collectively indicates that GPIb/IX-antibodies may be associated with an increased platelet hepatic sequestration and elevated TPO levels in severe thrombocytopenic ITP patients, however, further research is warranted to elucidate the pathophysiological mechanisms. |
| Haematologica |
ARID5B influences B cell development and function in mouse. In addition, increased mitochondrial oxygen consumption rate of naïve or stimulated B cells of Arid5bOE mice was observed, compared to wildtype counterparts. Taken together, our results indicate that ARID5B may play important role in B-cell development and function. |
Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia. In the 230 patients evaluated at diagnosis and intensively treated, high ABC activity was a predictive factor for primary resistance, and in multivariate analysis including full molecular data, an independent factor for event-freesurvival (p=0.0370). JC-1 +/- CsA assay could be used at diagnosis to predict AML ontogeny and to complete prognosis evaluation in addition to new molecular markers. |
Early expression of CD94 and loss of CD96 on CD8+ T cells after allogeneic SCT is predictive of subsequent relapse and survival. Furthermore, reduced expression of the activatory molecule CD96 was associated with 2.2 fold increased risk of relapse and 1.9 fold reduction in survival. This work identifies CD94 and CD96 as potential targets for CD8-directed immunotherapy in the very early phase following allogeneic transplantation with the potential to reduce long term relapse rates and improve patient survival. |
Relative impact of residual cytogenetic abnormalities and flow cytometric measurable residual disease on outcome after allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia. To examine how residual cytogenetic abnormalities and MRD testing by multiparameter flow cytometry (MFC) may refine risk assessment before HCT, we analyzed 506 adults with cytogenetically abnormal AML who underwent both routine karyotyping and MFC MRD testing before receiving a first allograft while in morphologic remission. Testing for residual cytogenetic abnormalities and MFC MRD identified four groups of patients with differential relapse-free survival (RFS, hazard ratio [HR]=1.63 for Cytoabnormal/MFCnegative [P=0.01, n=63], HR=3.24 for Cytonormal/MFCpositive [P. |
Translational readthrough at F8 nonsense variants in factor VIII B domain contributes to residual expression and lowers inhibitor association. These original findings into HA molecular genetics, and particularly into genotype-phenotype relationships related with disease treatment, demonstrate that B-domain features favour PTC readthrough output. This provides a potential molecular mechanism contributing to differential PTC-associated inhibitor occurrence, with translational implications for a novel, experimentally based classification of F8 nonsense variants. |
| Lancet Haematol |
Haploidentical bone marrow transplantation in patients with relapsed or refractory severe aplastic anaemia in the USA (BMT CTN 1502): a multicentre, single-arm, phase 2 trial. Attention to obtaining high cell doses (>2·5 |
| Leukemia |
ASXL1 mutations predict inferior molecular response to nilotinib treatment in chronic myeloid leukemia. Patients carrying an ASXL1 mutation at diagnosis showed a less favorable molecular response to nilotinib treatment, as a major molecular response (MMR) was achieved less frequently at month 12, 18, and 24 compared to al other patients. Patients with ASXL1 mutations were also younger and more frequently found in the high risk category, suggesting a central role of clonal evolution associated with ASXL1 mutations in CML pathogenesis. |
Droplet digital PCR for the detection of second-generation tyrosine kinase inhibitor-resistant BCR::ABL1 kinase domain mutations in chronic myeloid leukemia. Retrospective review of BCR::ABL1 NGS results in 513 consecutive CML patients with non-optimal response to first- or second-line TKI therapy suggested that a ddPCR-based approach targeted against 2GTKI-resistant mutations would score samples as mutation-negative in 22% of patients with warning response to imatinib but only in 6% of patients with warning response to 2GTKIs. We conclude ddPCR represents an attractive method for easy, accurate and rapid screening for 2GTKI-resistant mutations impacting on TKI selection, although ddPCR cannot identify compound mutations. |
Genomic landscape of patients with FLT3-mutated acute myeloid leukemia (AML) treated within the CALGB 10603/RATIFY trial. When evaluating two-fold variable combinations the most striking effects were found for WT1:NPM1 (with NPM1 mutation abrogating the negative effect of WT1 mutation), and for WT1:treatment (with midostaurin exerting a beneficial effect in WT1-mutated AML). This targeted gene sequencing study provides important, novel insights into the genomic background of FLT3-mutated AML including the prognostic impact of co-mutations, specific gene-gene interactions, and possible treatment effects of midostaurin. |
High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance. By multivariate analysis, CCSS by OGM only (not CBA), TP53 mutation and BM blasts independently predicted survival. This is the first and largest study reporting the value of combined SVP and NGS for MDS prognostication. |
Identification of proliferative and non-proliferative subpopulations of leukemic cells in CLL. As the quiescent sub-population precedes treatment, selection likely explains the persistence of such residual non-proliferating populations during BCR-antagonist therapy. These findings have clinical implications for discontinuation of long-term BCR-antagonist treatment in selected patients. |
Inhibition of the m6A reader IGF2BP2 as a strategy against T-cell acute lymphoblastic leukemia. Furthermore, we identified a small-molecule IGF2BP2 inhibitor JX5 and treatment of T-ALL with JX5 showed similar functions as knockdown of IGF2BP2. These findings not only shed light on the role of IGF2BP2 in T-ALL, but also provide an alternative |
Requirement for TP73 and genetic alterations originating from its intragenic super-enhancer in adult T-cell leukemia. Notably, recurrent deletions of TP73 exons 2-3 were observed in a fraction of primary ATL cases that harbored the super-enhancer, while induction of this deletion in cell lines further increased proliferation and mutational burden. Our study suggests that formation of the TP73 intragenic super-enhancer and genetic deletion are likely sequentially acquired in relation to intracellular state of ATL cells, which leads to functional alteration of TP73 that confers additional clonal advantage. |
SLIT2 promoter hypermethylation-mediated SLIT2-IT1/miR-218 repression drives leukemogenesis and predicts adverse prognosis in myelodysplastic neoplasm. In summary, our findings demonstrate that SLIT2 promoter hypermethylation is associated with disease evolution in MDS and predicts poor prognoses in both MDS and AML. Epigenetic inactivation of SLIT2-IT1/miR-218 by SLIT2 promoter hypermethylation could be a promising therapeutic target in MDS. |
| Thromb Haemost |
Anticoagulant Effects of Dabigatran on Coagulation Laboratory Parameters in Pediatric Patients: Combined Data from Five Pediatric Clinical Trials. The similar relationships of laboratory parameters observed across pediatric age groups suggests that developmental changes in the hemostatic system may have little effect on response to dabigatran. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
| CA Cancer J Clin |
The contemporary management of cancers of the sinonasal tract in adults. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded. |
| Lancet Haematol |
Packed red blood cell transfusion in preterm infants. Thus, neonatal transfusion practice has become an ongoing difficulty, in which differences in transfusion guidelines hinder the ability to generate comparable clinical data, and heterogeneity in clinical data prevents the implementation of standardised transfusion protocols. To overcome these issues, novel approaches with biochemical-clinical translational designs could enable clinicians to gather causal evidence instead of circumstantial correlation. |
Letters to the editors and authors’ replies
| J Hematol Oncol |
NBAS, a gene involved in cytotoxic degranulation, is recurrently mutated in pediatric hemophagocytic lymphohistiocytosis. According to our findings, NBAS is the second most frequently mutated gene (2.11%) in our HLH cohort after PRF1. NBAS deficiency may contribute to the development of HLH via a dysregulated lytic vesicle transport pathway. |
Oral eltanexor treatment of patients with higher-risk myelodysplastic syndrome refractory to hypomethylating agents. Overall, the most frequently reported treatment-related adverse events were nausea (45%), diarrhea (35%), decreased appetite (35%), fatigue and neutropenia (both 30%). Single-agent oral eltanexor was active, safe, and well tolerated in patients with higher-risk, primary HMA-refractory MDS. |
all remaining publications eg case reports, images of the month, etc…
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |
| Leukemia |
| Thromb Haemost |